Toward the Identification of Neurodevelopmental Risk Markers of Bipolar Disorder

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DESCRIPTION (provided by applicant): The educational aim of the proposed K01 proposal is to allow the applicant to train in developmental affective neuroscience and pediatric bipolar disorder and acquire the skills necessary to characterize neurodevelopmental abnormalities in neural systems of emotion regulation in young adolescents at high genetic risk of bipolar disorder. Bipolar disorder is a chronic and debilitating psychiatric disorder in adults and even more so in children and adolescents. It is characterized by significant impairments in emotion regulation, which have been associated with functional abnormalities in prefrontal and subcortical neural regions. Bipolar disorder may be mediated by neurodevelopmental abnormalities in these neural regions. The onset of bipolar disorder increases dramatically in adolescence, which is a key period for the development of prefrontal systems involved in modulating and regulating emotions. Studies in adolescent offspring of parents with bipolar disorder, who are significantly at risk of developing the illness, promise to help elucidate some of the neural mechanisms involved in the development of bipolar disorder. This proposal will use functional magnetic resonance imaging (fMRI) to investigate differences in neural activity associated with implicit emotional information processing and emotional cognitive control in young healthy adolescents at high genetic risk of bipolar disorder compared to low-risk controls. The secondary goal is to explore to what extent these differences in neural activity are associated with pubertal maturation. The central tenet of the proposed project is that reduced modulation of emotional information processing by higher-order cognitive control processes represents a key risk factor for bipolar disorder. This project complements the proposed career development plan that will involve obtaining training in: 1) developmental affective neuroscience approaches to the study of emotion regulation in adolescence, 2) clinical issues associated with pediatric bipolar disorder, 3) methodology used to examine neural systems of emotion regulation, including increased knowledge and skills in fMRI of neural systems at the interface of cognitive control and emotion and ethical issues associated with pediatric neuroimaging, 4) design and methods used in longitudinal research and advanced statistical techniques for modeling neurodevelopmental trajectories. Findings from this study will contribute to identifying potential neurodevelopmental risk markers for bipolar disorder and establishing endophenotypes of emotion dysregulation specific to bipolar disorder, which will facilitate the development of early intervention strategies.